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PMID: 11102524 Published · ppublish English Journal Article Research Support, U.S. Gov't, P.H.S.

The latent transforming growth factor-beta-binding protein-1 promotes in vitro differentiation of embryonic stem cells into endothelium.

Molecular biology of the cell ·Vol. 11 ·No. 12 ·2000-12-00 ·Pages 4295-308

Gualandris A, Annes JP, Arese M, Noguera I, Jurukovski V, Rifkin DB

Abstract

The latent transforming growth factor-beta-binding protein-1 (LTBP-1) belongs to a family of extracellular glycoproteins that includes three additional isoforms (LTBP-2, -3, and -4) and the matrix proteins fibrillin-1 and -2. Originally described as a TGF-beta-masking protein, LTBP-1 is involved both in the sequestration of latent TGF-beta in the extracellular matrix and the regulation of its activation in the extracellular environment. Whereas the expression of LTBP-1 has been analyzed in normal and malignant cells and rodent and human tissues, little is known about LTBP-1 in embryonic development. To address this question, we used murine embryonic stem (ES) cells to analyze the appearance and role of LTBP-1 during ES cell differentiation. In vitro, ES cells aggregate to form embryoid bodies (EBs), which differentiate into multiple cell lineages. We analyzed LTBP-1 gene expression and LTBP-1 fiber appearance with respect to the emergence and distribution of cell types in differentiating EBs. LTBP-1 expression increased during the first 12 d in culture, appeared to remain constant between d 12 and 24, and declined thereafter. By immunostaining, fibrillar LTBP-1 was observed in those regions of the culture containing endothelial, smooth muscle, and epithelial cells. We found that inclusion of a polyclonal antibody to LTBP-1 during EB differentiation suppressed the expression of the endothelial specific genes ICAM-2 and von Willebrand factor and delayed the organization of differentiated endothelial cells into cord-like structures within the growing EBs. The same effect was observed when cultures were treated with either antibodies to TGF-beta or the latency associated peptide, which neutralize TGF-beta. Conversely, the organization of endothelial cells was enhanced by incubation with TGF-beta 1. These results suggest that during differentiation of ES cells LTBP-1 facilitates endothelial cell organization via a TGF-beta-dependent mechanism.

MeSH Terms
Animals Antibodies/immunology Biomarkers Carrier Proteins/genetics,immunology,physiology Cell Differentiation Cells, Cultured Endothelium/cytology,embryology,metabolism Extracellular Matrix/metabolism Gene Expression Intracellular Signaling Peptides and Proteins Latent TGF-beta Binding Proteins Mice Stem Cells/cytology,metabolism Time Factors Transforming Growth Factor beta/immunology,physiology
Chemicals
Antibodies Biomarkers Carrier Proteins Intracellular Signaling Peptides and Proteins LTBP1 protein, human LTBP2 protein, human Latent TGF-beta Binding Proteins Ltbp1 protein, mouse Ltbp2 protein, mouse Transforming Growth Factor beta
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Gualandris A
Department of Cell Biology, New York University School of Medicine, New York, New York 10016-6497, USA.
Annes J P
Arese M
Noguera I
Jurukovski V
Rifkin D B
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Article Info
Journal
Molecular biology of the cell
Abbr.
Mol Biol Cell
ISSN
1059-1524
DOI
10.1091/mbc.11.12.4295
Published
2000-12-00
Pages
4295-308
Language
English
Region
United States
NLM ID
9201390
PMCID
PMC15073
Subset
IM
External Links
PubMed source DOI: 10.1091/mbc.11.12.4295 PMC Full Text View journal details
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